The objective of this research is to elucidate in vitro the in vivo cellular and regulatory defects which result in various human immune deficiency states. We intend to booster immunized patients in vivo with soluble tetanus toxoid and examine the in vitro kinetics of appearance in the circulation, and determine the numbers of functional subpopulations of anti-tetanus toxoid antibody producing B cells have previously been characterized in normal individuals and consists of 1) cells which secrete IgG anti-Tet without T-cell or mitogen requirements 2) cells which synthesize IgM anti-Tet with pokeweed mitogen and T-cell help and 3) cells which synthesize IgG anti-Tet in the presence of pokeweed mitogen and T-cell help 14-80 days after an obligatory in vivo booster immunization. The ability of the patients to generate these cells in vivo, and the functional capabilities of these cells in vitro will be correlated with appearance of antibodies in the serum and secretions. We will examine the role in immune deficiency of suppressor cells which contain a membrane receptor for adenosine which in normals can be activated to suppress IgG synthesis. Our hypothesis is that immune deficient individuals which fail to synthesize normal quantities of IgG in vitro contain abnormal numbers of these cells and that their removal will lead to normal in vitro IgG synthesis. If correct, we will use pharmacological agents in vitro in an attempt to reverse this suppression with the aim of future in vivo therapeutic modalities. We will also examine in vivo the production of autoantibodies against these suppressor cells and assess the immunoregulatory properties of these antibodies on in vitro immunoglobulin synthesis. Other studies will investigate the in vivo generation of antigen-specific suppressor cells and compare the number and activity of these cells in immune deficient patients with normal individuals. Finally in order to investigate immune regulatory defects not associated with the pokeweed mitogen stimulated lymphocytes we will employ other mitogens which stimulate different lymphocyte subsets and examine their role in immune deficiency. Methods employed include mitogen and antigen stimulation of lymphocytes enriched or depleted of lymphocyte subsets, followed by analysis of specific antibody and total immunoglobulin by radioimmunoassay.